Autonomic nervous system activity is essential for maintaining circulatory and metabolic homeostasis. In order to study sympathetic nervous system function and its relationship to other neuroendocrine systems, it is necessary to measure neurotransmitter, hormonal, and peptide levels in response to various stimuli. The levels of norepinephrine, epinephrine, and dopamine nd their metabolites in various body fluids reflect the activity of the neurones from which these neurotransmitters are released. Cerebrospinal fluid levels of monoamine metabolites can be used to assess central nervous system neurotransmitter metabolism. It is necessary to consider the origin of these metabolites to make appropriate corrections for valid interpretations of the data. These strategies have been used to study patients with neurogenic orthostatic hypotension and other disorders in which abnormal adrenergic function is suspected. Post-prandial hypotension may result from endogenous insulin release in response to a meal since patients with autonomic failure manifest a significant reduction in blood pressure during a euglycemic insulin test. Although blood pressure decreases following insulin administration in patients with autonomic failure, peripheral vascular resistance and venous compliance do not change. The ACTH response to arecoline, a cholinergic agonist, is reduced in patients with multiple system atrophy (MSA). Cerebrospinal fluid levels of acetylcholinesterase are also reduced in MSA. These results provide further support for central cholinergic involvement in MSA. In patients with pure autonomic failure (PAF), the increase in plasma gastrin during isoproterenol infusion is much greater than normal suggesting receptor supersensitivity of a beta-adrenergic mechanism mediating release of the hormone. A similar increase in cardiovascular responses to isoproterenol was observed in PAF. Urinary excretion of atrial natriuretic factor is increased in patients with autonomic failure. Supine and standing plasma norepinephrine levels were found in patients with thyroidectomy whose replacement therapy was withdrawn. A thorough understanding of neurotransmitter metabolism and peptide function in these clinical situations leads to more rational approaches to therapy. Several drug trials for managing orthostatic hypotension including further refinement of a sympathetic neural prosthesis are in progress.